Eun Y Lee

Publications (2)12 Total impact

• Article: Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis.

  Daiki Okamura, Marlene E Starr, Eun Y Lee, Arnold J Stromberg, B Mark Evers, Hiroshi Saito
  [show abstract] [hide abstract]
  ABSTRACT: The severity and mortality rates of acute pancreatitis (AP) are significantly elevated in the elderly population. However, due to a lack of appropriate animal models, the underlying mechanisms for this age-dependent vulnerability remain largely unknown. The purpose of this study was to characterize a murine model of AP, which displays age-associated severity, and to use this model to identify pathophysiologies that are distinctive of the aged with AP. AP was induced in young (4-5 months), middle-aged (12-13 months), and aged (23-25 months) C57BL/6 mice by repeated injection of caerulein, a homologue of the gastrointestinal hormone cholecystokinin. Approximately 10% of aged mice died during AP, while young and middle-aged mice showed no mortality. Although both young and aged mice exhibited early signs of edema and inflammation in the pancreas, kidney, and lung, young mice showed signs of recovery within 24 h, while aged mice exhibited increasingly severe tissue damage and cell death. There was a significant age-dependent increase in pancreatic neutrophil activation and systemic inflammation as assessed by pancreatic myeloperoxidase and plasma interleukin-6 (IL-6) concentration, respectively. Importantly, aged but not young mice with AP showed significantly elevated thrombosis in the lung and kidney as well as a marked increase in plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of the fibrinolytic system. These results demonstrate that aging is associated with increased severity of AP characterized by augmented and prolonged pancreatic inflammation and the presence of multiple extra-pancreatic sequelae including thrombosis.
  Aging cell 06/2012; 11(5):760-9. · 7.55 Impact Factor
• Source

  Available from: Xianglin Shi

  Article: Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway.

  Xin Wang, Ardhendu K Mandal, Hiroshi Saito, Joseph F Pulliam, Eun Y Lee, Zun-Ji Ke, Jian Lu, Songze Ding, Li Li, Brent J Shelton, Thomas Tucker, B Mark Evers, Zhuo Zhang, Xianglin Shi
  [show abstract] [hide abstract]
  ABSTRACT: Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway.
  Toxicology and Applied Pharmacology 04/2012; 262(1):11-21. · 4.45 Impact Factor